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Home / Publicações / Characterization of amino acids Arg, Ser and Thr at position 70 within HIV-1 reverse transcriptase

Characterization of amino acids Arg, Ser and Thr at position 70 within HIV-1 reverse transcriptase

  • Autores: Bernatchez J, Camacho RJ, Covens K, De Wit S, Dekeersmaeker N, Götte M, Megens S, Theys K, Van Laethem K, Vandamme AM, Vinken L
  • Ano de Publicação: 2014
  • Journal: Acta Clinica Belgica
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/25103592

Objectives:

The amino acid position 70 in HIV-1 reverse transcriptase (RT) plays an important role in nucleoside RT inhibitor (NRTI) resistance. K70R is part of the thymidine analog mutations, but also other amino acid changes have been associated with NRTI resistance, such as K70E and K70G. In this study, we investigated the in vivo selection of the HIV-1 RT mutations K70S and K70T and their in vitro effect on drug resistance and replication capacity.

Methods:

Recombinant viruses with RT mutations were generated to measure the in vitro drug susceptibility and replication capacity. Bayesian network analysis and three-dimensional modeling were performed to understand the selection and impact of the RT70 mutations.

Results:

K70S and K70T were found at a low frequency in RTI-experienced HIV-1 patients (0.10% and 0·20%). Baeyesian network learning identified no direct association with the in vivo exposure to any specific RTI. However, direct associations of K70S with mutations within the Q151M-complex and of K70T with K65R were observed. In vitro phenotypic testing revealed only minor effects of K70R/S/T as single mutations, associated with Q151M and within the context of the Q151M-complex.

Discussion:

These results suggest that the selection of K70S/T and their phenotypic impact are influenced by the presence of other mutations in RT. However, the low impact on in vitro phenotype here observed, alongside with the low in vivo prevalence, the exclusive direct association with known major RTI mutations and the unknown correlation with in vivo response, do not yet necessitate the inclusion of K70S/T in drug resistance interpretation systems.

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About GHTM

GHTM is a R&D Center that brings together researchers from IHMT with a track record in Tropical Medicine and International/Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

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